Virtual screening of plant-derived compounds against SARS-CoV-2 viral proteins using computational tools

Zígolo, María Antonela; Goytia, Matías Rivero; Poma, Hugo Ramiro; Rajal, Verónica Beatriz; Irazusta, Verónica Patricia

The new SARS-CoV-2, responsible for the COVID-19 pandemic, has been threatening public health worldwide for more than a year. The aim of this work was to evaluate compounds of natural origin, mainly from medicinal plants, as potential SARS-CoV-2 inhibitors through docking studies. The viral spike (S) glycoprotein and the main protease Mpro, involved in the recognition of virus by host cells and in viral replication, respectively, were the main molecular targets in this study. Molecular docking was performed using AutoDock, which allowed us to select the plant actives with the highest affinity towards the viral targets and to identify the interaction molecular sites with the SARS-CoV2 proteins. The best energy binding values for S protein were, in kcal/mol: −19.22 for glycyrrhizin, −17.84 for gitoxin, −12.05 for dicumarol, −10.75 for diosgenin, and − 8.12 for delphinidin. For Mpro were, in kcal/mol: −9.36 for spirostan, −8.75 for N-(3-acetylglycyrrhetinoyl)-2-amino-propanol, −8.41 for α-amyrin, −8.35 for oleanane, −8.11 for taraxasterol, and − 8.03 for glycyrrhetinic acid. In addition, the synthetic drugs umifenovir, chloroquine, and hydroxychloroquine were used as controls for S protein, while atazanavir and nelfinavir were used for Mpro. Key hydrogen bonds and hydrophobic interactions between natural compounds and the respective viral proteins were identified, allowing us to explain the great affinity obtained in those compounds with the lowest binding energies. These results suggest that these natural compounds could potentially be useful as drugs to be experimentally evaluated against COVID-19.